0000000000262613
AUTHOR
David L. Sacks
Skin-derived macrophages from Leishmania major-susceptible mice exhibit interleukin-12- and interferon-gamma-independent nitric oxide production and parasite killing after treatment with immunostimulatory DNA.
Co-administration of CpG-containing immunostimulatory oligodeoxynucleotides and parasite antigen protects susceptible BALB/c mice from otherwise progressive infection with Leishmania major. Although the protective effect of CpG-containing immunostimulatory oligodeoxynucleotides is clearly dependent on endogenous interleukin-12 and interferon-gamma production, the source of these Th1-promoting cytokines in infected mice is unknown. In contrast to macrophages from Leishmania-resistant C57BL/6 mice, macrophages from susceptible BALB/c mice are hyporesponsive to stimulation with lipopolysaccharide and interferon-gamma. While studying interactions of various antigen-presenting cells with Leishma…
Skin Dendritic Cells in Murine Cutaneous Leishmaniasis
Studies of the immunopathogenesis of Leishmania major-induced murine cutaneous leishmaniasis provide a framework for understanding the evolution of L. major infection of skin in humans and the foundation for rationale vaccine design. Experiments in which infection is initiated with "suprap hysiologic" numbers of parasites clearly identify Th-derived type I cytokines as essential participants in macrophage activation and macrophage nitric oxide production as prerequisite for parasite control. Dendritic cells, rather than macrophages, appear to be responsible for L. major-specific Th priming in these studies. Recent studies of murine cutaneous leishmaniasis in a model system in which infectio…
Leishmania major-infected murine Langerhans cell-like dendritic cells from susceptible mice release IL-12 after infection and vaccinate against experimental cutaneous Leishmaniasis
Leishmania major-infected C57BL / 6 skin-dendritic cells (DC) are activated and release cytokines (including IL-12 p70), and likely initiate protective Th1 immunity in vivo (von Stebut, E. et al., J. Exp. Med.188: 1547 – 1552). To characterize differences in DC function in mice that are genetically susceptible (BALB / c) and resistant (C57BL / 6) to cutaneous leishmaniasis, we analyzed the effects of L. major on Langerhans cell-like, fetal skin-derived DC (FSDDC) from both strains. BALB / c- and C57BL / 6-FSDDC ingested similar numbers of amastigotes, but did not ingest metacyclic promastigotes. Like C57BL / 6-FSDDC, infection of BALB / c-FSDDC led to up-regulation of MHC class I and II ant…